The studies described are designed to provide clues to the mechanism by which human polymorphonuclear neutrophils and monocytes sense and migrate directionally in response to a chemical gradient. Special emphasis is placed on identification and characterization of mechanisms by which leukocyte chemotaxis is modulated. Mechanisms associated with oxidative metabolisms, lysosomal enzyme secretion, prostaglandin synthesis and cellular adherence will be considered. Methods of study will include protocols to measure migratory and nonmigratory leukocyte functions, binding of chemotactic ligands, and morphological changes associated with binding of chemotactic agents. The results of these studies of normal leukocyte function will be applied to studies of patient leukocyte function and especially to identification of cellular defects in neutropenic individuals in two local families.